SF2523

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种新型有效的 PI3K 和 BRD4 双重抑制剂，对 BRD4 (BD1)、PI3Kα 和 PI3Kγ 的 IC50 分别为 241、34、158 nM。

A novel potent, dual inhibitor of PI3K and BRD4 with IC50 of 241, 34, 158 nM for BRD4 (BD1), PI3Kα and PI3Kγ, respectively; interacts robustly with the full-length BRD4 (Kd=140 nM) and BRD4(BD1) (Kd=150 nM), binds more weakly BRD4(BD2) (Kd = 710 nM); blocks MYC expression and activation, promotes MYC degradation, and markedly inhibits cancer cell growth and metastasis both in vitro and in vivo.

SF2523 treatment decreases protein levels of MYCN and Cyclin D1, the MYCN target, and inhibits AKT activation by blocking phosphorylation of AKT at Ser473. SF2523 treatment leads to the displacement of BRD4 from both MYCN promoter sites. SF2523 interacts robustly with the full-length BRD4 (Kd=140 nM) and exhibits comparable affinity to the BRD4 first BD (BD1) (Kd=150 nM), however it binds more weakly to the second BD (BD2) of BRD4 (Kd=710 nM). Comparison of binding affinities of SF2523 for BDs of other proteins reveal that it binds equally well to BDs of BRD4, BRD2, and BRD3; shows moderate binding to BDs of CECR2 and BRDT; but associates much weaker with other BDs.

SF2523 treatment results in a significant reduction of tumor volume compared with control. Importantly, SF2523 shows no gross toxicity to the treated mice, as there is no notable change in body weight. Tumors from SF2523-treated mice have markedly reduced MYCN, pAKT, and Cyclin D1 levels compared with levels of these proteins in vehicle-treated mice tumors.

SF-2523 | SF 2523

PI3K/Akt/mTOR signaling

PI3K

BRD4|DNA-PK|mTOR|PI3Kα|PI3Kγ

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1174428-47-7

371.40698

C19H17NO5S

>98% (HPLC)

DMSO: ≥ 30 mg/mL

O=C1C=C(N2CCOCC2)OC3=C1SC=C3C4=CC=C(OCCO5)C5=C4

7H-Thieno[3,2-b]pyran-7-one, 3-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-(4-morpholinyl)-

(-20℃)

With Ice Pack

≥ 2 years